Antibodies point to bat bite survival

By Amanda Alvarez, Milwaukee Journal Sentinel •August 2, 2012 9:18 pm

MILWAUKEE — Jeanna Giese, the Fond du Lac native who was the world’s first unvaccinated rabies survivor, has some company. A new study reports at least nine other people have antibodies that indicate survival of a rabid bat bite.

The discovery of this enhanced immune response to rabies has important implications for understanding and future treatment of the disease, which is usually 100 percent fatal.

Rabies kills an estimated 55,000 people worldwide each year. Only one or two of those cases are in the United States, thanks to aggressive vaccination of livestock and pets.

Bats are a major reservoir of the rabies virus in the U.S, and in Peru, where the new study was conducted, vampire bats spread the disease, feeding on humans when other warm-blooded victims are not available.

Only 1 percent of vampire bats are rabid and infectious, says Amy Gilbert, lead author of the study and an ecologist at the U.S. Centers for Disease Control and Prevention’s National Center for Emerging and Zoonotic Infectious Diseases. This small proportion of bats has nonetheless been responsible for numerous rabies outbreaks in the Amazon.

Gilbert and colleagues interviewed 92 people in northern Peru and gathered blood samples from two-thirds of them. More than half reported previous bat bites, and nine individuals were found to have rabies antibodies; only one person had been previously vaccinated. The work was published Wednesday in the American Journal of Tropical Medicine and Hygiene.

“(These) people were highly exposed to not just vampire bat bites, but to rabid bat bites and the virus,” Gilbert said. “The most reasonable explanation is that these people are exposed to low doses of virus or have repeated exposures over their lifetime . . . as older people are more likely to be seropositive (test positive for virus antibodies).”

The study participants did not report that they had ever experienced clinical symptoms of rabies, but Gilbert says they can’t be sure whether these individuals had survived infections without taking samples of cerebrospinal fluid.

“There are a variety of factors that can influence the likelihood of whether viral exposure leads to infection,” Gilbert explained. “Host genetic makeup, dose, the severity of the bite, the location of the bite” can determine whether the rabies virus reaches the central nervous system and causes a full-blown infection, which is nearly universally fatal.

The rabies virus is often able to sneak by the immune system and head to the nerves. The authors of the study speculate that if “dirty bites” occurred in the Peruvian cases, the immune response could be activated due to other non-rabies germs, helping to clear the virus at the same time.

What happens in such a mild or unsuccessful infection is “the golden question in terms of treatment and therapeutics,” according to Gilbert. “It has happened so few times that we just don’t know well enough what specific factor is responsible for infection aborting once in the central nervous system.”

Rodney Willoughby, the Children’s Hospital and Medical College of Wisconsin doctor who developed Jeanna Giese’s lifesaving treatment, said in an e-mail that Gilbert’s study is “potentially a game-changer, because it implies that rabies is not always severe or fatal.”

The “Milwaukee protocol” — an induced coma and powerful antiviral drugs used experimentally to treat rabies — has been used in 44 cases since Giese faced rabies in 2004; there have been five survivors, according to Willoughby.

For those who are at high risk of rabies, such as children in the Amazon, Willoughby and Gilbert hope for greater awareness, such as avoiding unknown animals, and inclusion of the vaccine in routine immunizations.

“It’s exciting to think that . . . humans can mount an immune response and fight infection off in the periphery (of the body),” said Gilbert. “One hypothesis we cannot rule out is that there are genetic factors or natural selection for enhanced immune response, but we don’t have evidence for or against this.”

Further study could uncover why these unique individuals didn’t develop the disease, leading to more effective treatments, she said.